Friday, December 7, 2012

Fungi That Will Make Your Skin Crawl

by Lev Ostrer

An interesting and unexpected discovery was made in 1998 about a Chytridiomycota family of fungi that had taken scientists by storm. Prior to this discovery the Chitrid family was believed to be a family of decomposing fungi that lived on dead animals and other decomposing matter(1), but this was all about to change with a discovery of a new family member, Batrachochytrium dendrobatidis.
Unlike the rest of the family, B. dendrobatidis prefers to live inside
living things. Primarily it lives inside amphibian skin of frogs, toads and
even salamanders. This clever fungus figured out a way to get under the skin
and live there while spitting out large amounts of motile zoospores, which
infect more amphibians that share the same water source. The incredibly mobile
zoospores can also be picked up by birds and animals and moved to other bodies of
water. Though might be a great survival strategy for the fungus many species of
amphibians die due to the fungus thriving under their skin.

Fig 1. 2 types of cells
in the frogs’ epithelium, principal and amitochondria cell. A principal cell
is using pores to uptake water,

and ATPase to move K+ from plasma and Na+ into
the plasma.

Mitochondria rich cell uses pores to uptake Cl- and ATPase

to K+
and Na+.

For many organisms that have skin, skin’s primary job
is to keep unwanted things out and to keep the insides safe; however for frogs,
skin is much more than a protective barrier. For frogs skin is also used as a
way to keep hydrated and a way to breathe. Up to 90% of the frog’s epidermal
surface is made up of cells called principal cells (1). These cells play an
important role in electrolyte and water transport using a variety of channels
and ATPases (transport proteins that use ATP to move molecules against
chemical/concentration gradient) to achieve proper K+ and Na+ concentration within the organism (fig1). The other 10% of epidermal cells are mitochondria rich cells that are also involved in transport of electrolytes, but these cells specialize in Na+ and CL- transport. When Batrachochytrium dendrobatidis invades the skin, it inserts itself under the top layer of epidermis and begins producing keratin. Keratin is the main component of hair and nails, so in effect the infected frog has hair/nail like material growing under its skin. The worst part is that this causes the top layer of skin to peel off (fig2), which in turn causes a frog to experience reduction of Na+ absorption, as well as, a drop of K+ and Cl- in plasma. This will eventually result in a heart attack due to skewed electrical gradient (2). While K+ and Cl- levels are falling, during late stages of infection, a frog is also experiencing extreme dehydration, which cause amphibian to spend more time near water thus releasing more zoospores into environment. The infection is directly related to the fungus life cycle, where keratin is made in order to promote zoospore release.

Batrachochytrium dendrobatidis has an interesting life
cycle that can be broken down in two phases; Substrate-independent (a free
swimming zoospore) and substrate-dependent (where it invades a host) (fig3). A
young zoospore is equipped with flagella, and after leaving zoosporangium it
has about 24 hours to attach to a host. Once it attaches several changes take
place. First it loses its motility by retracting its flagella, and begins
making a wall of chitin around the spore. At the same time a germination tube
begins to form, which penetrates the top epithelial layer and injects it’s
contains into a host. This causes a formation of a cyst under the skin of the
frog. The cyst stays in the deeper skin tissue until it matures. A mature cyst
then begins producing keratin in order to form a barrier to separate
zoosporangium from the germination tube. Due to the loss of skin cells, a host
frog begins to make more skin cells, causing a mature cyst to move outwards,
towards the newly formed epithelial layer (2). Once zoosporangium (cyst)
reaches the surface a plug on the surface of the cyst gets removed and new
generation of motile zoospores leaves ready to infect nearby cells as well as
other amphibian inhabitants of the ecosystem (fig3). As more cells become
infected, keratin production goes up, eventually causing chunks of skin to fall
off (fig2), finally resulting in the host’s death.

However the story
doesn’t end here; frogs are finding clever ways of fighting back the fungus.
Many neotropical species of steam-dwelling harlequin toads and frogs such as A.
elegans that live in lowlands at 25C°
are beginning to show a great amount of resistance against the B.
dendrobatidis. In part, this is due
to the high temperature of 25 C° at which fungus grows slower allowing for more
time to mount an immune response before full spread infection. This is not
surprising because a life cycle of Bd, is very temperature sensitive, where fungus thrives between 4-23C°, and
it dies when temperature is over 28C °or under 4C°.The colder temperature gets in its healthy range, the
longer it takes for cyst to mature, and the warmer it is the faster zoospores
are produced (4). On top of temperature being in the frogs’ favor, harlequin
toads and frogs were found to grow their own antifungal medication (3).
Scientist went out and swabbed the skin of 3 different members of the Atelopus
(harlequin toads and frogs common to
Central and South America) family that showed an increased resistance to Bd.
Of 148 swabbed bacterial species
isolated 26% turned out to have antifungal properties. One particular species
of frogs stood out by far from all the others based on its ability to fight off
the fungus.40%of bacteria found on A.elegans skin had antifungal activity. This species,
interestingly enough was also the only species that tested positive for the
fungus. This indicated that A. elegans had undergone a natural selection event, where members of the species
without antifungal bacteria died off, and ones that remained had an increased
amount of antifungal bacteria on its skin.

Thus
the battle continues, between parasitic fungi and frogs. Hopefully it soon will
come to the end since many amphibian species that are dying from the infection
are in danger of going extinct. Fortunately species like A.elegans are showing the way this fungus can be slowed, if not
stopped.Maybe endangered frogs
can take a lesson from A. elegans,
and if needed with a little help from humans harness the power of antifungal
bacteria to prevent extinction.

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